TISSUE-CULTURE STUDIES OF HUMAN ORAL CARCINOMA 1. PROLIFERATIVE CAPACITIES OF NON-MALIGNANT AND MALIGNANT ORAL EXPLANTS.
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A 7-year-old spayed female Siamese cat was presented with a 7-day history of ataxia, circling to the right, and involuntary micturition and defecation. Cerebrospinal fluid analysis showed increased protein content and relative eosinophilia. At necropsy, there was flattening of the cerebral cortical gyri of the right frontal and parietal lobes, and both kidneys had multiple wedge-shaped cortical indentations. Histologically, the cerebral cortex contained several extensive malacic foci, and the kidneys had multifocal parenchymal degeneration and atrophy. There was multifocal partial to complete thrombosis of renal interlobar arteries and of the right middle cerebral artery and meningeal branches; these thrombi contained large anaplastic round cells, which often invaded the arterial wall. Many smaller vessels within the kidneys and brain were occluded with clusters of similar cells, without thrombosis or vascular wall invasion. The neoplastic round cells had immunohistochemical staining properties of T lymphocytes.
Deoxypyridinium (DPD) cross-links are a specific parameter for collagen type I degradation. We report the longitudinal tracking of DPD in relation to other bone markers and imaging techniques in a patient with osteomalacia and secondary hyperparathyroidism from reduced light exposure due to attire. This patient was first admitted for diffuse skeletal pain. X-rays showed general demineralization and Looser's transformation zones in the neck of the left femur. MRI examinations of the pelvis and the proximal femora demonstrated bilateral signs of acute sacroiliitis, as well as edema-like lesions in the femoral heads and necks bilaterally. The baseline parathyroid hormone level was 8 times higher than the normal upper limit, whereas 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were significantly reduced. A 7-fold increase in free urinary DPD and a 17-fold increase in bone-specific alkaline phosphatase (bone-AP) were also measured. Percutaneous transiliac bone biopsy revealed markedly increased osteoidosis. Osteomalacia was diagnosed due to chronically reduced sun exposure caused by restrictive attire, and cholecalciferol substitution therapy was begun. After a follow-up of 28 weeks, non-specific parameters of bone turnover (parathyroid hormone, total alkaline phosphatase, serum calcium and serum phosphate) had normalized, while DPD, as a specific bone degradation marker, and bone-AP, as a bone formation parameter, both remained elevated. This example underlines the validity of DPD and bone-AP as indicators of increased bone metabolism: not only were they the parameters with the highest baseline deviation, but they were also the last to normalize.
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The kinetics of neutral amino acid transport were examined in isogeneic matched pairs of hybrid cells, one member of each pair being tumorigenic, the other not. The L system of transport, which is sodium-independent, was measured by the uptake of leucine, and the A system, which is sodium-dependent, by the uptake of methylaminoisobutyric acid. Although there was variation from one cell type to another in both Km and Vmax for the transport of these amino acids, no systematic change was found to be associated with tumorigenicity. This is in marked contrast with hexose uptake where tumorigenicity was invariably found to be associated with a reduction in Km. It thus appears that whatever molecular change is responsible for the alteration in the kinetics of hexose transport, it is specific, at least to the extent that it does not affect either sodium-dependent or sodium-independent transport of neutral amino acids.
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